Involving patients in therapy development: Lessons learned from Duchenne exon skipping скачать в хорошем качестве

Involving patients in therapy development: Lessons learned from Duchenne exon skipping

The importance of involving patients in therapy development: Lessons learned from Duchenne exon skipping Duchenne muscular dystrophy is a progressive muscle wasting disease that occurs in ~1 in 5000 newborn boys. The disease is caused by pathogenic variants that disrupt the open reading frame of the dystrophin gene. The dystrophin protein provides muscle fibers with stability during exercise by connecting the actin cytoskeleton to the extracellular matrix. Lacking dystrophin, Duchenne patients suffer from accumulating muscle damage, which eventually results in loss of muscle tissue and function. When pathogenic variants maintain the open reading frame, internally deleted but partially functional dystrophins can be produced. These variants are found in Becker muscular dystrophy, which has a later onset and slower progression compared to Duchenne. The exon skipping approach aims to allow Duchenne patients to make Becker-like dystrophins. This is achieved with antisense oligonucleotides (ASOs) that target specific exons during pre-mRNA splicing of dystrophin transcripts. Skipping an exon will enlarge the deletion, but restore the reading frame. Proof-of-concept for ASO-mediated dystrophin restoration was provided in cultured cells, animal models and patients. See our upcoming webinars: https://www.oligotherapeutics.org/web...